Structure of cytoplasmic ring of nuclear pore complex by integrative cryo-EM and AlphaFold

The nuclear pore complex (NPC) is the conduit for bidirectional cargo traffic between the cytoplasm and the nucleus. We determined a near-complete structure of the cytoplasmic ring of the NPC from Xenopus oocytes using single-particle cryo-electron microscopy and AlphaFold prediction. Structures of nucleoporins were predicted with AlphaFold and fit into the medium-resolution map by using the prominent secondary structural density as a guide. Certain molecular interactions were further built or confirmed by complex prediction by using AlphaFold. We identified the binding modes of five copies of Nup358, the largest NPC subunit with Phe-Gly repeats for cargo transport, and predicted it to contain a coiled-coil domain that may provide avidity to assist its role as a nucleation center for NPC formation under certain conditions.

Automated summary

This study determined the near-complete structure of the cytoplasmic ring of the nuclear pore complex (NPC) using cryo-electron microscopy and AlphaFold prediction. Molecular interactions and the binding modes of Nup358, the largest NPC subunit, were also predicted. The findings shed light on the formation and function of the NPC.